TNFBR (TNFR75) is the larger of the 2 TNF receptors. It is present on many cell types, especially those of myeloid origin, and is strongly expressed on stimulated T and B lymphocytes.
NCBI Summary:
The protein encoded by this gene is a member of the TNF-receptor superfamily. This protein and TNF-receptor 1 form a heterocomplex that mediates the recruitment of two anti-apoptotic proteins, c-IAP1 and c-IAP2, which possess E3 ubiquitin ligase activity. The function of IAPs in TNF-receptor signalling is unknown, however, c-IAP1 is thought to potentiate TNF-induced apoptosis by the ubiquitination and degradation of TNF-receptor-associated factor 2, which mediates anti-apoptotic signals. Knockout studies in mice also suggest a role of this protein in protecting neurons from apoptosis by stimulating antioxidative pathways. [provided by RefSeq, Jul 2008]
General function
Receptor
Comment
Cellular localization
Plasma membrane
Comment
candidate123
Ovarian function
Follicle atresia
Comment
Molecular Cloning of Porcine (Sus scrofa) Tumor Necrosis Factor Receptor 2. Cheng Y et al. Tumor necrosis factor (TNF) alpha can induce both cell death and proliferation by binding to either TNF receptor (TNFR) 1 or 2. In the granulosa cells of porcine ovaries, TNFalpha is considered to act as an anti-apoptotic/survival factor during follicular atresia. As a first step toward elucidating the function of TNFR2 in regulating follicular development/growth and atresia in porcine ovaries, we isolated the porcine (Sus scrofa) cDNA encoding TNFR2, which was identified from a cDNA library prepared from the follicular granulosa cells of pig ovaries. Porcine TNFR2 (1,125 bp, 375 amino acid residues), which contains specific amino acid region of transmembrane, indicated high identities with human and murine TNFR2 (78 and 69% at mRNA level, respectively; 73 and 61% at protein level, respectively), suggesting that the function of porcine TNFR2 is similar to that of human and murine homologues. Understanding the expression patterns of porcine TNFR2 mRNA in various organs, which we confirmed by reverse transcription polymerase chain reaction analysis, would help to elucidate the physiological role of TNFR2 in the regulation of apoptosis in porcine organs.
Expression regulated by
Comment
Ovarian localization
Granulosa
Comment
Nakayama M, et al 2003 reported changes in the Expression of Tumor Necrosis Factor (TNF) alpha, TNFalpha Receptor (TNFR) 2, and TNFR-Associated Factor 2 in Granulosa Cells During Atresia in Pig Ovaries.
Tumor necrosis factor (TNF) alpha can induce both cell death and cell proliferation and exerts its effects by binding to either TNF receptor (TNFR) 1 or 2. When TNFalpha-bound TNFR2 interacts with TNFR-associated factor 2 (TRAF2), expression of survival/antiapoptotic genes is up-regulated. In the present study the author determined the changes in localization of TNFalpha and TRAF2 and their mRNAs and the expression of TNFR2 in granulosa cells during follicular atresia in pig ovaries. In healthy follicles, intense signals for TNFalpha and TRAF2 and their mRNAs were demonstrated in the outer zone of the granulosa layer, where many proliferating cells and no apoptotic cells were observed. In atretic follicles, decreased or trace staining for TRAF2 and its mRNA and decreased expression of TNFR2 were observed in the granulosa layer, where many apoptotic cells were seen. These findings suggested that TNFalpha acts as a survival factor in granulosa cells during follicular atresia in pig ovaries.
Follicle stages
Antral
Comment
Phenotypes
PCO (polycystic ovarian syndrome)
Mutations
1 mutations
Species: human
Mutation name: type: naturally occurring fertility: subfertile Comment: Comment: the methionine 196 arginine polymorphism in exon 6 of the TNF receptor 2 gene (TNFRSF1B) is associated with the polycystic ovary syndrome and hyperandrogenism. Peral B et al. (2002) Inflammatory cytokines such as TNF alpha may play a role in the pathogenesis of common metabolic disorders, including hyperandrogenism and the polycystic ovary syndrome (PCOS). The TNF receptor 2 mediates most of the metabolic effects of TNF alpha. In the present study, we have evaluated serum soluble TNF receptor 2 levels, and several common polymorphisms in the TNF receptor 2 gene (TNFRSF1B), in women presenting with PCOS or hyperandrogenic disorders. Initial studies included 103 hyperandrogenic patients (42 presenting with PCOS) and 36 controls from Spain. The 196R alleles of the M196R (676 T-->G) variant in exon 6 of TNFRSF1B, which is in linkage disequilibrium with a CA-repeat microsatellite polymorphism in intron 4 of TNFRSF1B, tended to be more frequent in hyperandrogenic patients than in controls (P = 0.056), reaching statistical significance when the analysis was restricted to include only PCOS patients (P < 0.03). Extended analysis including another 11 hyperandrogenic patients from Spain and 64 patients and 29 controls from Italy confirmed the association between 196R alleles of the M196R variant and hyperandrogenic disorders (P < 0.05), which was maintained when restricting the analysis to PCOS patients (P < 0.02). On the contrary, the 3'-untranslated region (exon 10) variants 1663 G-->A, 1668 T-->G, and 1690 T-->C were not associated with hyperandrogenism. The soluble TNF receptor 2 levels were not different between patients and controls but were increased in obese subjects, compared with lean individuals, and were affected by the interaction between the 1663 G-->A and 1668 T-->G variants in the 3'-untranslated region of TNFRSF1B. The TNFRSF1B genotype did not influence any clinical or biochemical variable related to hyperandrogenism or insulin sensitivity and was not associated with obesity, both in hyperandrogenic patients and healthy controls considered separately. In conclusion, the M196R (676 T-->G) variant in exon 6 of TNFRSF1B is associated with hyperandrogenism and PCOS, further suggesting a role for inflammatory cytokines in the pathogenesis of these disorders.//////////////////